A 62-year-old woman presents to the hospital with shortness of breath. She has a history of HIV infection and was recently hospitalized for PCP pneumonia and was discharged 3 days ago in stable condition on oral antibiotics. After discharge, she started to experience a headache and subsequently developed worsening shortness of breath. The rest of her medical history is significant for hypertension, diabetes, peripheral arterial disease, hypothyroidism, and gastroesophageal reflux disease (GERD). Her regular medications include aspirin, amlodipine, hydrochlorothiazide, metformin, levothyroxine, and pantoprazole. She has not been compliant with her antiretrovirals. Her allergies include trimethoprim–sulfamethoxazole and penicillin. She drinks alcohol moderately and has a 30 pack-year smoking history. On examination, she has a temperature of 37.6°C, blood pressure of 158/96 mmHg, heart rate of 86 beats per minute, and respiratory rate of 26 breaths per minute. There are no murmurs or jugular venous distention, and there are no wheezes or rales on pulmonary examination. There is blue discoloration of her digits and lips. An arterial blood gas shows a normal PaO2, although the blood has a brownish discoloration.
Which of the following is the most likely diagnosis?A. Chronic obstructive pulmonary disease
Methemoglobinemia. The differential of dyspnea is broad, but it can be narrowed based on the history and physical examination (even in a complicated patient like this one!). The two broad categories that can be considered first are pulmonary and cardiovascular disease. Pulmonary disease may be broken down into airway disease (e.g., bronchitis, asthma, bronchiectasis, tumor), parenchymal disease (e.g., interstitial lung disease, pulmonary edema), or pleural disease (e.g., pleural effusion). Important cardiovascular diseases that cause dyspnea include left heart failure, pulmonary hypertension, pulmonary embolism, and vasculitides affecting the pulmonary vasculature.
In addition to these two categories, there are neuromuscular causes (e.g., myasthenic crisis), metabolic causes (e.g., metabolic acidosis), psychological causes (e.g., panic disorder), and causes relating to the oxygen-carrying capacity of the blood. The diagnosis in this case relates to this last category. Methemoglobinemia may be congenital or acquired, and certain medications such as dapsone and nitric oxide can cause methemoglobinemia. The pathophysiology involves oxidation of iron to the ferric state (Fe3+ ), which cannot bind oxygen but causes the other heme groups in hemoglobin to bind oxygen more tightly, shifting the hemoglobin dissociation curve to the left. The result is an inability of the circulating hemoglobin to provide oxygen to tissues. PaO2 will be normal and the pulse oximetry will typically be in the 85% to 89% range. The blood is sometimes described as “chocolate blood” due to its dark red or brown appearance. Treatment is with methylene blue, an agent that reduces Fe3+ back to Fe2+ . This patient likely has methemoglobinemia secondary to dapsone, since dapsone is an alternative to trimethoprim–sulfamethoxazole for the treatment of PCP pneumonia.
(A, B, C, D) The rest of these conditions, except for carbon monoxide poisoning, would have a depressed PaO2. (D) Carbon monoxide poisoning may present with headache and cyanosis due to carbon monoxide displacing oxygen from heme and reducing the oxygen carrying capacity of the blood. Pulse oximetry and PaO2 will be normal in this condition.